MMP/TIMP imbalance in amniotic fluid during PROM: An indirect support for endogenous pathway to membrane rupture

Stephen J. Fortunato, Ramkumar Menon, Salvatore J. Lombardi

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Objective: We theorize that excessive degradation of the fetal membrane extracellular matrix (ECM) by specific matrix metalloproteinases (MMPs) results in preterm premature rupture of the membranes (PROM). Active, inhibitor free MMP2 and 9 (gelatinase A and B respectively) can degrade the amniochorion basement membrane Type IV collagen to initiate rupture. This study examines the levels of the gelatinases and their natural inhibitors (tissue inhibitor of matrix metalloproteinases -TIMPs) in the amniotic fluid during PROM, preterm labor (PTL) and at term. Methods: A total of 51 AF samples were collected from the following groups of patients. Group I: Women with PTL and no ROM (n = 16) Group 2: Women with PROM (n = 16) irrespective of labor status Group 3: Women at term with intact membranes undergoing cesarean delivery irrespective of labor status (n = 19). ELISA was used to assay MMP2, MMP9, TIMP1 and TIMP2 levels in the amniotic fluid. The active, TIMP free levels of MMP2 were quantitated by zymography followed by computerized densitometry. Active MMP9 was measured using a bioassay that specifically detects MMP9 activity. Statistical analysis was performed by Tukey-Kramer multiple comparison method. Results: PROM is associated with increased MMP2 levels (mean 2125 ng/ml;) when compared with term (mean 1455 ng/ml; p < 0.01) or PTL where a non significant increase was seen (mean 1862 ng/ml; p = ns). MMP9 levels were higher in PROM (mean 15.03 ng/ml) than at term (mean 1.14 ng/ml; p < 0.001) or PTL (mean 3.75 ng/ml; p < 0.01). TIMP1 levels were slightly increased during PROM (mean 3143 ng/ml) compared to term (mean 1892 ng/ ml, p < 0.05) pr PTL where a non significant change was seen (mean 2406 ng/ml; p = ns). TLMP2 levels were decreased in PROM (mean 98 ng/ml) compared with term (mean 176 ng/ml; p < 0.05) and PTL (mean 236 ng/ml; p < 0.001). Active, TIMP free MMP2 levels were increased during PROM (mean 233 pg/ ml) compared to those at term (mean 132 pg/ml; p < 0.05) or PTL (mean 132 pg/ml; p < 0.05). Active forms of MMP9 were seen only during PROM (mean 632 pg/ml). Conclusion: Active, TIMP free forms of MMP2 and 9 are increased in the amniotic fluid of women with PROM. These MMPs can degrade the amniochorion basement membranes and other ECM components resulting in FROM.

Original languageEnglish (US)
Pages (from-to)362-368
Number of pages7
JournalJournal of Perinatal Medicine
Volume27
Issue number5
StatePublished - 1999
Externally publishedYes

Fingerprint

Amniotic Fluid
Matrix Metalloproteinases
Rupture
Premature Obstetric Labor
Membranes
Extracellular Matrix
Tissue Inhibitor of Metalloproteinases
Extraembryonic Membranes
Gelatinases
Collagen Type IV
Densitometry
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Basement Membrane
Biological Assay
Enzyme-Linked Immunosorbent Assay

Keywords

  • Amniotic fluid
  • Gelatinases
  • Imbalance
  • Premature rupture of membranes
  • Preterm labor
  • Timps

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Pediatrics, Perinatology, and Child Health

Cite this

MMP/TIMP imbalance in amniotic fluid during PROM : An indirect support for endogenous pathway to membrane rupture. / Fortunato, Stephen J.; Menon, Ramkumar; Lombardi, Salvatore J.

In: Journal of Perinatal Medicine, Vol. 27, No. 5, 1999, p. 362-368.

Research output: Contribution to journalArticle

@article{72ee076aa6994de0aa090a1e68a7c480,
title = "MMP/TIMP imbalance in amniotic fluid during PROM: An indirect support for endogenous pathway to membrane rupture",
abstract = "Objective: We theorize that excessive degradation of the fetal membrane extracellular matrix (ECM) by specific matrix metalloproteinases (MMPs) results in preterm premature rupture of the membranes (PROM). Active, inhibitor free MMP2 and 9 (gelatinase A and B respectively) can degrade the amniochorion basement membrane Type IV collagen to initiate rupture. This study examines the levels of the gelatinases and their natural inhibitors (tissue inhibitor of matrix metalloproteinases -TIMPs) in the amniotic fluid during PROM, preterm labor (PTL) and at term. Methods: A total of 51 AF samples were collected from the following groups of patients. Group I: Women with PTL and no ROM (n = 16) Group 2: Women with PROM (n = 16) irrespective of labor status Group 3: Women at term with intact membranes undergoing cesarean delivery irrespective of labor status (n = 19). ELISA was used to assay MMP2, MMP9, TIMP1 and TIMP2 levels in the amniotic fluid. The active, TIMP free levels of MMP2 were quantitated by zymography followed by computerized densitometry. Active MMP9 was measured using a bioassay that specifically detects MMP9 activity. Statistical analysis was performed by Tukey-Kramer multiple comparison method. Results: PROM is associated with increased MMP2 levels (mean 2125 ng/ml;) when compared with term (mean 1455 ng/ml; p < 0.01) or PTL where a non significant increase was seen (mean 1862 ng/ml; p = ns). MMP9 levels were higher in PROM (mean 15.03 ng/ml) than at term (mean 1.14 ng/ml; p < 0.001) or PTL (mean 3.75 ng/ml; p < 0.01). TIMP1 levels were slightly increased during PROM (mean 3143 ng/ml) compared to term (mean 1892 ng/ ml, p < 0.05) pr PTL where a non significant change was seen (mean 2406 ng/ml; p = ns). TLMP2 levels were decreased in PROM (mean 98 ng/ml) compared with term (mean 176 ng/ml; p < 0.05) and PTL (mean 236 ng/ml; p < 0.001). Active, TIMP free MMP2 levels were increased during PROM (mean 233 pg/ ml) compared to those at term (mean 132 pg/ml; p < 0.05) or PTL (mean 132 pg/ml; p < 0.05). Active forms of MMP9 were seen only during PROM (mean 632 pg/ml). Conclusion: Active, TIMP free forms of MMP2 and 9 are increased in the amniotic fluid of women with PROM. These MMPs can degrade the amniochorion basement membranes and other ECM components resulting in FROM.",
keywords = "Amniotic fluid, Gelatinases, Imbalance, Premature rupture of membranes, Preterm labor, Timps",
author = "Fortunato, {Stephen J.} and Ramkumar Menon and Lombardi, {Salvatore J.}",
year = "1999",
language = "English (US)",
volume = "27",
pages = "362--368",
journal = "Journal of Perinatal Medicine",
issn = "0300-5577",
publisher = "Walter de Gruyter GmbH & Co. KG",
number = "5",

}

TY - JOUR

T1 - MMP/TIMP imbalance in amniotic fluid during PROM

T2 - An indirect support for endogenous pathway to membrane rupture

AU - Fortunato, Stephen J.

AU - Menon, Ramkumar

AU - Lombardi, Salvatore J.

PY - 1999

Y1 - 1999

N2 - Objective: We theorize that excessive degradation of the fetal membrane extracellular matrix (ECM) by specific matrix metalloproteinases (MMPs) results in preterm premature rupture of the membranes (PROM). Active, inhibitor free MMP2 and 9 (gelatinase A and B respectively) can degrade the amniochorion basement membrane Type IV collagen to initiate rupture. This study examines the levels of the gelatinases and their natural inhibitors (tissue inhibitor of matrix metalloproteinases -TIMPs) in the amniotic fluid during PROM, preterm labor (PTL) and at term. Methods: A total of 51 AF samples were collected from the following groups of patients. Group I: Women with PTL and no ROM (n = 16) Group 2: Women with PROM (n = 16) irrespective of labor status Group 3: Women at term with intact membranes undergoing cesarean delivery irrespective of labor status (n = 19). ELISA was used to assay MMP2, MMP9, TIMP1 and TIMP2 levels in the amniotic fluid. The active, TIMP free levels of MMP2 were quantitated by zymography followed by computerized densitometry. Active MMP9 was measured using a bioassay that specifically detects MMP9 activity. Statistical analysis was performed by Tukey-Kramer multiple comparison method. Results: PROM is associated with increased MMP2 levels (mean 2125 ng/ml;) when compared with term (mean 1455 ng/ml; p < 0.01) or PTL where a non significant increase was seen (mean 1862 ng/ml; p = ns). MMP9 levels were higher in PROM (mean 15.03 ng/ml) than at term (mean 1.14 ng/ml; p < 0.001) or PTL (mean 3.75 ng/ml; p < 0.01). TIMP1 levels were slightly increased during PROM (mean 3143 ng/ml) compared to term (mean 1892 ng/ ml, p < 0.05) pr PTL where a non significant change was seen (mean 2406 ng/ml; p = ns). TLMP2 levels were decreased in PROM (mean 98 ng/ml) compared with term (mean 176 ng/ml; p < 0.05) and PTL (mean 236 ng/ml; p < 0.001). Active, TIMP free MMP2 levels were increased during PROM (mean 233 pg/ ml) compared to those at term (mean 132 pg/ml; p < 0.05) or PTL (mean 132 pg/ml; p < 0.05). Active forms of MMP9 were seen only during PROM (mean 632 pg/ml). Conclusion: Active, TIMP free forms of MMP2 and 9 are increased in the amniotic fluid of women with PROM. These MMPs can degrade the amniochorion basement membranes and other ECM components resulting in FROM.

AB - Objective: We theorize that excessive degradation of the fetal membrane extracellular matrix (ECM) by specific matrix metalloproteinases (MMPs) results in preterm premature rupture of the membranes (PROM). Active, inhibitor free MMP2 and 9 (gelatinase A and B respectively) can degrade the amniochorion basement membrane Type IV collagen to initiate rupture. This study examines the levels of the gelatinases and their natural inhibitors (tissue inhibitor of matrix metalloproteinases -TIMPs) in the amniotic fluid during PROM, preterm labor (PTL) and at term. Methods: A total of 51 AF samples were collected from the following groups of patients. Group I: Women with PTL and no ROM (n = 16) Group 2: Women with PROM (n = 16) irrespective of labor status Group 3: Women at term with intact membranes undergoing cesarean delivery irrespective of labor status (n = 19). ELISA was used to assay MMP2, MMP9, TIMP1 and TIMP2 levels in the amniotic fluid. The active, TIMP free levels of MMP2 were quantitated by zymography followed by computerized densitometry. Active MMP9 was measured using a bioassay that specifically detects MMP9 activity. Statistical analysis was performed by Tukey-Kramer multiple comparison method. Results: PROM is associated with increased MMP2 levels (mean 2125 ng/ml;) when compared with term (mean 1455 ng/ml; p < 0.01) or PTL where a non significant increase was seen (mean 1862 ng/ml; p = ns). MMP9 levels were higher in PROM (mean 15.03 ng/ml) than at term (mean 1.14 ng/ml; p < 0.001) or PTL (mean 3.75 ng/ml; p < 0.01). TIMP1 levels were slightly increased during PROM (mean 3143 ng/ml) compared to term (mean 1892 ng/ ml, p < 0.05) pr PTL where a non significant change was seen (mean 2406 ng/ml; p = ns). TLMP2 levels were decreased in PROM (mean 98 ng/ml) compared with term (mean 176 ng/ml; p < 0.05) and PTL (mean 236 ng/ml; p < 0.001). Active, TIMP free MMP2 levels were increased during PROM (mean 233 pg/ ml) compared to those at term (mean 132 pg/ml; p < 0.05) or PTL (mean 132 pg/ml; p < 0.05). Active forms of MMP9 were seen only during PROM (mean 632 pg/ml). Conclusion: Active, TIMP free forms of MMP2 and 9 are increased in the amniotic fluid of women with PROM. These MMPs can degrade the amniochorion basement membranes and other ECM components resulting in FROM.

KW - Amniotic fluid

KW - Gelatinases

KW - Imbalance

KW - Premature rupture of membranes

KW - Preterm labor

KW - Timps

UR - http://www.scopus.com/inward/record.url?scp=0032741989&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032741989&partnerID=8YFLogxK

M3 - Article

C2 - 10642956

AN - SCOPUS:0032741989

VL - 27

SP - 362

EP - 368

JO - Journal of Perinatal Medicine

JF - Journal of Perinatal Medicine

SN - 0300-5577

IS - 5

ER -